Acute Pharmacotherapy of Unipolar Psychotic Depression

Summary

Principal Investigator: Alastair Flint
Affiliation: University of Toronto
Country: Canada
Abstract: Psychotic depression (PD) is a severe disorder that is present in 20% of mixed-age inpatients and in more than 40% of elderly inpatients hospitalized for the treatment of major depression. Acutely, PD is associated with a greater level of depression severity, functional impairment, and resistance to antidepressant treatment than nonpsychotic depression. Longitudinally, PD is associated with a greater likelihood of recurrence, a shorter symptom-free interval, greater disability, and an increased long-term risk of suicide. Among elderly patients, PD has also been associated with a high one year mortality rate. Although electroconvulsive therapy (ECT) is a highly effective treatment for PD, pharmacotherapy is more easily administered and generally preferred by many patients and psychiatrists. Furthermore, ECT is less available to, and less frequently used by minority ethnic groups, patients with low incomes, and those residing in rural areas. In the early 1980's a landmark NIMH randomized controlled trial demonstrated that a combination of high doses of both a tertiary amine tricyclic and a conventional antipsychotic was more efficacious than monotherapy with either medication. However, this combination has been associated with a high incidence of significant side effects, particularly in elderly patients. This collaborative U01 project builds on findings from the four sites principal investigators and others. Based on preliminary studies suggesting that sertraline, a serotonin-reuptake-inhibitor (SSRI) and olanzapine, an atypical antipsychotic, may be effective in the acute treatment of PD, this study uses a two-armed randomized double-blind parallel-group design to compare the efficacay and tolerability of combining these two medications to olanzapine alone. By blocking recruitment of subjects age greater than or equal to 60 on a 1:1 basis the study will determine the relationship between older age and remission, time to remission and tolerability. A 12-week acute phase efficacy study is followed by a 20-week continuation trial during which subjects who achieved partial remission enter a placebo-controlled augmentation trial that is based on their initial assignment. Remitted subjects are also followed during stabilization to determine the stability of remission and predictors of clinical and functional deterioration.
Funding Period: 2002-09-06 - 2008-05-31
more information: NIH RePORT

Top Publications

  1. ncbi A delusion assessment scale for psychotic major depression: Reliability, validity, and utility
    Barnett S Meyers
    Department of Psychiatry, Weill Medical College of Cornell University, New York Presbyterian Hospital Westchester Division, West Chester, New York 10605, USA
    Biol Psychiatry 60:1336-42. 2006
  2. ncbi Persisting low use of antipsychotics in the treatment of major depressive disorder with psychotic features
    Carmen Andreescu
    Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    J Clin Psychiatry 68:194-200. 2007
  3. ncbi Missed diagnosis of psychotic depression at 4 academic medical centers
    Anthony J Rothschild
    Department of Psychiatry, University of Massachusetts Medical School, and UMass Memorial Healthcare, Worcester, MA 01605, USA
    J Clin Psychiatry 69:1293-6. 2008
  4. ncbi Weight gain during olanzapine treatment for psychotic depression: effects of dose and age
    Eric Smith
    Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Int Clin Psychopharmacol 23:130-7. 2008
  5. ncbi Correlates of suicidality among patients with psychotic depression
    Ayal Schaffer
    Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
    Suicide Life Threat Behav 38:403-14. 2008
  6. ncbi A double-blind randomized controlled trial of olanzapine plus sertraline vs olanzapine plus placebo for psychotic depression: the study of pharmacotherapy of psychotic depression (STOP-PD)
    Barnett S Meyers
    Department of Psychiatry, Weill Medical College of Cornell University and New York Presbyterian Hospital, Westchester Division, White Plains, New York 10605, USA
    Arch Gen Psychiatry 66:838-47. 2009

Scientific Experts

  • B S Meyers
  • A J Rothschild
  • Ayal Schaffer
  • Eric Smith
  • Melynda Caswell
  • Alastair J Flint
  • Catherine Peasley-Miklus
  • Benoit H Mulsant
  • Moonseong Heo
  • Carmen Andreescu
  • Eros Papademetriou
  • Ellen M Whyte
  • Catherine Peasley Miklus

Detail Information

Publications6

  1. ncbi A delusion assessment scale for psychotic major depression: Reliability, validity, and utility
    Barnett S Meyers
    Department of Psychiatry, Weill Medical College of Cornell University, New York Presbyterian Hospital Westchester Division, West Chester, New York 10605, USA
    Biol Psychiatry 60:1336-42. 2006
    ..The development and assessment of the Delusional Assessment Scale (DAS) are described...
  2. ncbi Persisting low use of antipsychotics in the treatment of major depressive disorder with psychotic features
    Carmen Andreescu
    Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    J Clin Psychiatry 68:194-200. 2007
    ..We assessed the extent to which the pharmacotherapy received by patients with MD-Psy under usual care conforms to these recommendations...
  3. ncbi Missed diagnosis of psychotic depression at 4 academic medical centers
    Anthony J Rothschild
    Department of Psychiatry, University of Massachusetts Medical School, and UMass Memorial Healthcare, Worcester, MA 01605, USA
    J Clin Psychiatry 69:1293-6. 2008
    ..Major depressive disorder with psychotic features (psychotic depression), though occurring relatively frequently in the general population, is a commonly missed psychiatric diagnosis...
  4. ncbi Weight gain during olanzapine treatment for psychotic depression: effects of dose and age
    Eric Smith
    Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Int Clin Psychopharmacol 23:130-7. 2008
    ..14-1.05 kg). Cumulative olanzapine dose was also significantly associated with weight gain (P<0.0001). Approximately 60% of completers of the 12-week trial experienced clinically significant weight gain (> or =7% of baseline weight)...
  5. ncbi Correlates of suicidality among patients with psychotic depression
    Ayal Schaffer
    Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
    Suicide Life Threat Behav 38:403-14. 2008
    ..These findings reinforce the evidence that patients with psychotic depression are at high risk for suicide and underscore the importance of examining correlates of suicidality specific to patients with psychotic depression...
  6. ncbi A double-blind randomized controlled trial of olanzapine plus sertraline vs olanzapine plus placebo for psychotic depression: the study of pharmacotherapy of psychotic depression (STOP-PD)
    Barnett S Meyers
    Department of Psychiatry, Weill Medical College of Cornell University and New York Presbyterian Hospital, Westchester Division, White Plains, New York 10605, USA
    Arch Gen Psychiatry 66:838-47. 2009
    ..Evidence for the efficacy of combination pharmacotherapy has been limited and without positive trials in geriatric patients with major depression (MD) with psychotic features...